Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
Nodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without matern...
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doaj-87063948fe844905b26349e7389574382021-05-05T13:56:15ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.28183Vg1-Nodal heterodimers are the endogenous inducers of mesendodermTessa G Montague0https://orcid.org/0000-0002-5918-6327Alexander F Schier1https://orcid.org/0000-0001-7645-5325Department of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United States; Center for Brain Science, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United States; Harvard Stem Cell Institute, Cambridge, United States; FAS Center for Systems Biology, Harvard University, Cambridge, United StatesNodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without maternally provided vg1 fail to form endoderm and head and trunk mesoderm, and closely resemble nodal loss-of-function mutants. Although Nodal is processed and secreted without Vg1, it requires Vg1 for its endogenous activity. Conversely, Vg1 is unprocessed and resides in the endoplasmic reticulum without Nodal, and is only secreted, processed and active in the presence of Nodal. Co-expression of Nodal and Vg1 results in heterodimer formation and mesendoderm induction. Thus, mesendoderm induction relies on the combination of two TGF-beta-related signals: maternal and ubiquitous Vg1, and zygotic and localized Nodal. Modeling reveals that the pool of maternal Vg1 enables rapid signaling at low concentrations of zygotic Nodal.https://elifesciences.org/articles/28183TGF-betaNodal signalingheterodimerVg1Mesodermendoderm |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tessa G Montague Alexander F Schier |
spellingShingle |
Tessa G Montague Alexander F Schier Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm eLife TGF-beta Nodal signaling heterodimer Vg1 Mesoderm endoderm |
author_facet |
Tessa G Montague Alexander F Schier |
author_sort |
Tessa G Montague |
title |
Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm |
title_short |
Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm |
title_full |
Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm |
title_fullStr |
Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm |
title_full_unstemmed |
Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm |
title_sort |
vg1-nodal heterodimers are the endogenous inducers of mesendoderm |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2017-11-01 |
description |
Nodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without maternally provided vg1 fail to form endoderm and head and trunk mesoderm, and closely resemble nodal loss-of-function mutants. Although Nodal is processed and secreted without Vg1, it requires Vg1 for its endogenous activity. Conversely, Vg1 is unprocessed and resides in the endoplasmic reticulum without Nodal, and is only secreted, processed and active in the presence of Nodal. Co-expression of Nodal and Vg1 results in heterodimer formation and mesendoderm induction. Thus, mesendoderm induction relies on the combination of two TGF-beta-related signals: maternal and ubiquitous Vg1, and zygotic and localized Nodal. Modeling reveals that the pool of maternal Vg1 enables rapid signaling at low concentrations of zygotic Nodal. |
topic |
TGF-beta Nodal signaling heterodimer Vg1 Mesoderm endoderm |
url |
https://elifesciences.org/articles/28183 |
work_keys_str_mv |
AT tessagmontague vg1nodalheterodimersaretheendogenousinducersofmesendoderm AT alexanderfschier vg1nodalheterodimersaretheendogenousinducersofmesendoderm |
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1721460506801209344 |